Finding the missing honey bee genes: lessons learned from a genome upgrade

BACKGROUND: The first generation of genome sequence assemblies and annotations have had a significant impact upon our understanding of the biology of the sequenced species, the phylogenetic relationships among species, the study of populations within and across species, and have informed the biology of humans. As only a few Metazoan genomes are approaching finished quality (human, mouse, fly and worm), there is room for improvement of most genome assemblies. The honey bee (Apis mellifera) genome, published in 2006, was noted for its bimodal GC content distribution that affected the quality of the assembly in some regions and for fewer genes in the initial gene set (OGSv1.0) compared to what would be expected based on other sequenced insect genomes. RESULTS: Here, we report an improved honey bee genome assembly (Amel_4.5) with a new gene annotation set (OGSv3.2), and show that the honey bee genome contains a number of genes similar to that of other insect genomes, contrary to what was suggested in OGSv1.0. The new genome assembly is more contiguous and complete and the new gene set includes ~5000 more protein-coding genes, 50% more than previously reported. About 1/6 of the additional genes were due to improvements to the assembly, and the remaining were inferred based on new RNAseq and protein data. CONCLUSIONS: Lessons learned from this genome upgrade have important implications for future genome sequencing projects. Furthermore, the improvements significantly enhance genomic resources for the honey bee, a key model for social behavior and essential to global ecology through pollination.Funding for the project was provided by a grant to RG from the National Human Genome Research Institute, National Institutes of Health (NHGRI, NIH) U54 HG003273. Contributions from members of the CGE lab were supported by Agriculture and Food Research Initiative Competitive grant no. 2010- 65205-20407 from the USDA National Institute of Food Agriculture. AKB was supported by a Clare Luce Booth Fellowship at Georgetown University

The Multisite Violence Prevention Project: Impact of a Universal School-Based Violence Prevention Program on Social-Cognitive Outcomes

This study evaluated the impact of a universal school-based violence prevention program on social-cognitive factors associated with aggression and nonviolent behavior in early adolescence. The effects of the universal intervention were evaluated within the context of a design in which two cohorts of students at 37 schools from four sites (N=5,581) were randomized to four conditions: (a) a universal intervention that involved implementing a student curriculum and teacher training with sixth grade students and teachers; (b) a selective intervention in which a family intervention was implemented with a subset of sixth grade students exhibiting high levels of aggression and social influence; (c) a combined intervention condition; and (d) a no-intervention control condition. Short-term and long-term (i.e., 2-year post-intervention) universal intervention effects on social-cognitive factors targeted by the intervention varied as a function of students' pre-intervention level of risk. High-risk students benefited from the intervention in terms of decreases in beliefs and attitudes supporting aggression, and increases in self-efficacy, beliefs and attitudes supporting nonviolent behavior. Effects on low-risk students were in the opposite direction. The differential pattern of intervention effects for low- and high-risk students may account for the absence of main effects in many previous evaluations of universal interventions for middle school youth. These findings have important research and policy implications for efforts to develop effective violence prevention programs

Comparison of smoking-related DNA methylation between newborns from prenatal exposure and adults from personal smoking.

Aim: Cigarette smoking influences DNA methylation genome wide, in newborns from pregnancy exposure and in adults from personal smoking. Whether a unique methylation signature exists for in utero exposure in newborns is unknown. Materials & methods: We separately meta-analyzed newborn blood DNA methylation (assessed using Illumina450k Beadchip), in relation to sustained maternal smoking during pregnancy (9 cohorts, 5648 newborns, 897 exposed) and adult blood methylation and personal smoking (16 cohorts, 15907 participants, 2433 current smokers). Results & conclusion: Comparing meta-analyses, we identified numerous signatures specific to newborns along with many shared between newborns and adults. Unique smoking-associated genes in newborns were enriched in xenobiotic metabolism pathways. Our findings may provide insights into specific health impacts of prenatal exposure on offspring

Migrating from PVM to MPI, part I: The Unify System

This paper presents a new kind of portability system, Unify, which modifies the PVM message passing system to provide (currrently a subset of) the Message Passing Interface (MPI) standard notation for message passing. Unify is designed to reduce the effort of learning MPI while providing a sensible means to make use of MPI libraries and MPI calls while applications continue to run in the PVM environment. We are convinced that this strategy will reduce the costs of porting completely to MPI, while providing a gradual environment within which to evolve. Furthermore, it will permit immediate use of MPI-based parallel libraries in applications, even those that use PVM for user code. We describe several paradigms for supporting MPI and PVM message passing notations in a single environment, and note related work on MPI and PVM implementations. We show the design options that existed within our chosen paradigm (which is an MPI interface added to the base PVM system), and why we chose that par..

A Boundary Representation Solid Modelling Data Structure for General Numerical Grid Generation

The purpose of this thesis is to develop a topology data structure that supports both structured and unstructured grid generation methods. This topology data structure directly supports the method of building edge grids, surface grids and volume grids in order to construct high quality computational fluid dynamics (CFD) grids. The minimal topological information needed for computing both structured and unstructured grids is used to determine that a non manifold boundary representation topology data structure must be used. A search of published data structures led to the adoption of the radial edge non manifold (RENM) boundary representation data structure as the basis for our implementation. An explanation of the data structure details as well as behavior of the data structures is presented. The grid topology modelling (GTM) data structure has been implemented and is used in two different production grid generation systems, SolidMesh and GUM B. Several examples of high quality CFD grids are presented

Phenotypic complementation of genetic immunodeficiency by chronic herpesvirus infection

Variation in the presentation of hereditary immunodeficiencies may be explained by genetic or environmental factors. Patients with mutations in HOIL1 (RBCK1) present with amylopectinosis-associated myopathy with or without hyper-inflammation and immunodeficiency. We report that barrier-raised HOIL-1-deficient mice exhibit amylopectin-like deposits in the myocardium but show minimal signs of hyper-inflammation. However, they show immunodeficiency upon acute infection with Listeria monocytogenes, Toxoplasma gondii or Citrobacter rodentium. Increased susceptibility to Listeria was due to HOIL-1 function in hematopoietic cells and macrophages in production of protective cytokines. In contrast, HOIL-1-deficient mice showed enhanced control of chronic Mycobacterium tuberculosis or murine γ-herpesvirus 68 (MHV68), and these infections conferred a hyper-inflammatory phenotype. Surprisingly, chronic infection with MHV68 complemented the immunodeficiency of HOIL-1, IL-6, Caspase-1 and Caspase-1;Caspase-11-deficient mice following Listeria infection. Thus chronic herpesvirus infection generates signs of auto-inflammation and complements genetic immunodeficiency in mutant mice, highlighting the importance of accounting for the virome in genotype-phenotype studies

Phenotypic complementation of genetic immunodeficiency by chronic herpesvirus infection.

Variation in the presentation of hereditary immunodeficiencies may be explained by genetic or environmental factors. Patients with mutations in HOIL1 (RBCK1) present with amylopectinosis-associated myopathy with or without hyper-inflammation and immunodeficiency. We report that barrier-raised HOIL-1-deficient mice exhibit amylopectin-like deposits in the myocardium but show minimal signs of hyper-inflammation. However, they show immunodeficiency upon acute infection with Listeria monocytogenes, Toxoplasma gondii or Citrobacter rodentium. Increased susceptibility to Listeria was due to HOIL-1 function in hematopoietic cells and macrophages in production of protective cytokines. In contrast, HOIL-1-deficient mice showed enhanced control of chronic Mycobacterium tuberculosis or murine γ-herpesvirus 68 (MHV68), and these infections conferred a hyper-inflammatory phenotype. Surprisingly, chronic infection with MHV68 complemented the immunodeficiency of HOIL-1, IL-6, Caspase-1 and Caspase-1;Caspase-11-deficient mice following Listeria infection. Thus chronic herpesvirus infection generates signs of auto-inflammation and complements genetic immunodeficiency in mutant mice, highlighting the importance of accounting for the virome in genotype-phenotype studies